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Updated: Sep 12, 2025

Mapping Genome-wide Accessible Chromatin in Primary Human T Lymphocytes by ATAC-Seq

Mapping Genome-wide Accessible Chromatin in Primary Human T Lymphocytes by ATAC-Seq

Published on: November 13, 2017

一种自动化的ATAC-seq方法揭示了在开放色素中转录因子剂量反应的序列决定因素

Betty B Liu¹, Masaru Shimasawa², Sidney Vermeulen³

¹Department of Bioengineering, Stanford University, Stanford, CA, US.

bioRxiv : the preprint server for biology

|August 8, 2025

概括

了解转录因子 (TF) 剂量对基因调节的影响至关重要. 这项研究引入了RoboATAC来绘制TF水平如何改变染色质可访问性和基因表达的地图,揭示了基于序列的剂量敏感性.

科学领域:

分子生物学分子生物学
基因组学就是基因组学.
系统生物学系统生物学

背景情况:

转录因子 (TF) 剂量极大地影响细胞的身份.
TF剂量与染色质可访问性/基因表达之间的定量关系尚不清楚.

研究的目的:

开发一个可扩展的,自动化平台 (RoboATAC) 高通量染色体可访问性概况.
系统地研究分级TF过度表达对全基因组染色质可访问性和基因表达的影响.

主要方法:

开发了RoboATAC,一个自动化的ATAC-seq平台.
在HEK293T细胞中 (246个样本) 进行了由22 TFs的分级过度表达引起的染色质可访问性和基因表达变化的高通量分析.
利用深度学习模型和核细胞定位分析来解释TF剂量效应.

主要成果:

观察到染色质可访问性和TF足迹的剂量依赖性变化.
DNA序列准确地预测了可访问元素的剂量敏感性;低亲和度的动机需要更高的TF水平.
深度学习模型将图案定向,间距和侧面基点确定为影响可访问性的关键因素.
发现了两种不同的TF-依赖的核细胞定位模式,影响了可访问性.

结论:

TF剂量可以定量调节染色质的可访问性和基因表达.
DNA序列模式及其安排是TF剂量灵敏性的关键决定因素.
核动力学在TF剂量依赖的染色质调节中起着重要作用.

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